HPSE p.Ala352=
c.1056G>A · rs139839221 · VCV3056339
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.54%, mid)
Conditions
1
HPSE-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.4 |
| Overall | ||
| CADD | 0.059 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.54%
Middle Eastern · 214/6,040 alleles
Filtering AF
3.15%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3%
Overall
2.37%
38,190/1,613,968 alleles · low-frequency
exomes 35,557/1,461,674 · genomes 2,633/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 3.54% | 28 |
| Amishnot grpmax-eligible | 3.18% | 31 |
| European (non-Finnish) | 2.84% | 35 |
| Remaining individualsnot grpmax-eligible | 2.28% | 44 |
| Finnishnot grpmax-eligible | 1.83% | 55 |
| Admixed American | 1.39% | 72 |
| Ashkenazi Jewishnot grpmax-eligible | 1.22% | 82 |
| African / African-American | 0.412% | 243 |
| South Asian | 0.327% | 306 |
| East Asian | 0.00223% | 44,880 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- HPSE
- Protein
- p.Ala352=
- Coding
- c.1056G>A
- MANE Select
- NM_001098540
- dbSNP
- rs139839221
- Type
- single nucleotide variant
- Location
- chr4:83308880 (GRCh38)
- Gene constraint
- LOEUF 1.066 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.02 · 58 PDB
- Residue 352
- the 'required for heterodimerization with the heparanase 8 kda subunit' region
Disease context
HPSE-related disorder
Similar variants
- HPSE p.Asn459= Benign same condition
- HPSE p.Asp476Glu Likely benign same condition
- HPSE p.His436= Likely benign same condition
- HPSE p.Lys161Gln Benign same condition
- HPSE p.Lys307Arg Benign same condition
- HPSE p.Phe236Cys Likely benign same condition
- HPSE c.673+8C>A Benign ★★ same type
- HPSE p.Gly370Asp Likely benign ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/hpse-p-ala352 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown